1. Field of the Invention
The present invention relates generally to monitoring the status of neoplastic diseases. More particularly, it relates to a method for determining likelihood of patient survival and time to relapse for neoplastic diseases, particularly breast and ovarian adenocarcinomas.
The ability to monitor neoplastic disease status can be of great value. In addition to improving prognostication, knowledge of the disease status allows the attending physician to select the most appropriate therapy for the individual patient. For example, patients with a high likelihood of relapse can be treated rigorously, usually involving systemic chemotherapy and/or radiation therapy. When there is a lesser likelihood of relapse, less aggressive therapies can be chosen. Because of the severe patient distress caused by the more aggressive therapy regimens, it would be desirable to distinguish with a high degree of certainty those patients requiring such aggressive therapies.
Unfortunately, no single factor or combination of factors in human breast cancer is completely reliable in assessing disease status. While the degree of tumor involvement in lymph nodes or distant sites (tissues) generally provides the best correlation with likelihood of survival and time to relapse, the determination can only be made after the disease has progressed to the point of such involvement. Other factors, such as primary tumor size, hormonal status of the tumor, and the like, provide additional information, but still fall short of providing the desired reliability and early detection capability.
In the case of breast adenocarcinomas, the decision for chemotherapy after surgical removal of the tumor is usually based on the number of lymph nodes affected. A determination of nodal status, however, is still insufficient to confidently predict the status of the disease.
It would therefore be desirable to provide alternative factors which can be measured in order to determine the status of neoplastic diseases in human patients, particularly breast and ovarian adenocarcinomas. It would be further desirable if such factors provided a high correlation with disease status and allowed for determination of status at an early stage in the disease.
2. Description of the Background Art
A human proto-oncogene appearing to have tyrosine kinase activity was independently identified by three research groups: Semba et al. (1985) Proc. Natl. Acad. Sci. USA 82:6497-6501 (designating the gene c-erbB-2); Coussens et al. (1985) Science 230:1132-1139 (designating the gene HER2); and King et al. (1985) Science 229:974-976. Hereinafter, this gene is referred to as HER-2/neu. A related rat gene
(designated neu) was reported in Schecter et al. (1985) Science 229:976-978. Amplification of the gene and/or increased translation of expression of the gene have been observed in tumor cells and cell lines. See, e.g., Fukushige et al. (1986) Mol. Cell. Biol. 6:955-958 where amplification and elevated expression (mRNA) of the gene was observed in the MKN-7 gastric cancer cell line; Coussens et al. (1985) supra., where elevated transcription of the gene was observed in cell lines from a hepatoblastoma, a Ewing sarcoma, a rhabdomyosarcoma, two neuroblastomas, and a Wilms tumor; and King et al. (1985) supra., where amplification of the gene was observed in a mammary carcinoma cell line. Yokota et al. (1986) Lancet I:765-767 disclose amplification of the HER-2/neu gene observed in breast, kidney, and stomach adenocarcinomas. Akiyama et al. (1986) Science 232:1644-1646 discloses the preparation of antibodies against a synthetic 14 amino acid fragment of the HER-2/neu gene product. The antibodies were used to isolate and characterize the gene product as it is expressed in MKN-7 adenocarcinoma cells.